Towards designing globular antimicrobial peptide mimics: role of polar functional groups in biomimetic ternary antimicrobial polymers
Towards designing globular antimicrobial peptide mimics: role of polar functional groups in biomimetic ternary antimicrobial polymers
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设计球状抗菌肽模拟物：极性官能团在仿生三元抗菌聚合物中的作用
DOI：
10.1039/d0sm01896a
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发表时间：
2021
期刊：
影响因子：
3.4
通讯作者：
Vemparala, Satyavani
中科院分区：
文献类型：
--
作者：
Rani, Garima;Kuroda, Kenichi;Vemparala, Satyavani
利用原子分子动力学模拟，我们研究了由带电阳离子、疏水性和中性极性基团组成的三元甲基丙烯酸酯聚合物与模型细菌膜的相互作用。我们的模拟数据表明，随机三元聚合物可以深入渗透到膜内部，即使是单一聚合物的分配也会对膜结构产生显着影响。聚合物结合上的脂质重组显示出三元聚合物对阴离子 POPG 脂质具有很强的亲和力，并且与二元聚合物的对照情况（仅阳离子和疏水基团）相比也是如此。虽然二元聚合物在膜插入时表现出强烈的获得两亲构象的倾向，但我们的结果强烈表明，在无规三元聚合物的情况下不存在这种两亲构象。三元聚合物采用更加折叠的构象，在膜法线方向上保持排列，随后更深入地渗透到膜内部，这表明了一种没有两亲构象的新型膜分配机制。最后，我们还研究了三元聚合物聚集体与模型细菌膜的相互作用，结果表明，用极性基团取代一些疏水基团会导致弱保持的三元聚集体，使它们能够快速分配并插入膜内部。因此，我们的工作强调了将极性基团纳入传统二元仿生抗菌聚合物框架中的作用，并提出了不同的细菌膜划分模式，模仿防御素等球状抗菌肽的抗菌机制。
Using atomistic molecular dynamics simulations, we study the interaction of ternary methacrylate polymers, composed of charged cationic, hydrophobic and neutral polar groups, with model bacterial membrane. Our simulation data shows that the random ternary polymers can penetrate deep into the membrane interior and partitioning of even a single polymer has a pronounced effect on the membrane structure. Lipid reorganization, on polymer binding, shows a strong affinity of the ternary polymer for anionic POPG lipids and the same is compared with the control case of binary polymers (only cationic and hydrophobic groups). While binary polymers exhibit strong propensity of acquired amphiphilic conformations upon membrane insertion, our results strongly suggest that such amphiphilic conformations are absent in the case of random ternary polymers. The ternary polymers adopt a more folded conformation, staying aligned in the direction of the membrane normal and subsequently penetrating deeper into the membrane interior suggesting a novel membrane partitioning mechanism without amphiphilic conformations. Finally, we also examine the interactions of ternary polymer aggregates with model bacterial membranes, which show that replacing some of the hydrophobic groups by polar groups leads to weakly held ternary aggregates enabling them to undergo rapid partitioning and insertion into membrane interior. Our work thus underscores the role of inclusion of polar groups into the framework of traditional binary biomimetic antimicrobial polymers and suggests different mode of partitioning into bacterial membranes, mimicking antimicrobial mechanism of globular antimicrobial peptides like Defensin.
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影响因子：
3.3
作者：
Klauda, Jeffery B.;Venable, Richard M.;Freites, J. Alfredo;O'Connor, Joseph W.;Tobias, Douglas J.;Mondragon-Ramirez, Carlos;Vorobyov, Igor;MacKerell, Alexander D., Jr.;Pastor, Richard W.
通讯作者：
Pastor, Richard W.
β-肽与膜的序列依赖性相互作用。
DOI：
10.1021/jp1070242
发表时间：
2010
期刊：
The journal of physical chemistry. B
影响因子：
--
作者：
Jagannath Mondal;Xiao Zhu;Q. Cui;A. Yethiraj
通讯作者：
A. Yethiraj
影响因子：
2.9
作者：
Jean-Francois, Frantz;Castano, Sabine;Dufourc, Erick J.
通讯作者：
Dufourc, Erick J.
影响因子：
3.4
作者：
Horn, Joshua N.;Sengillo, Jesse D.;Lin, Dejun;Romo, Tod D.;Grossfield, Alan
通讯作者：
Grossfield, Alan
影响因子：
6.2
作者：
Colak, Semra;Nelson, Christopher F.;Nusslein, Klaus;Tew, Gregory N.
通讯作者：
Tew, Gregory N.